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Slitrk2 controls excitatory synapse development via PDZ-mediated protein interactions
Members of the Slitrk (Slit- and Trk-like protein) family of synaptic cell-adhesion molecules control excitatory and inhibitory synapse development through isoform-dependent extracellular interactions with leukocyte common antigen-related receptor protein tyrosine phosphatases (LAR-RPTPs). However,...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6863843/ https://www.ncbi.nlm.nih.gov/pubmed/31745231 http://dx.doi.org/10.1038/s41598-019-53519-1 |
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author | Han, Kyung Ah Kim, Jinhu Kim, Hyeonho Kim, Dongwook Lim, Dongseok Ko, Jaewon Um, Ji Won |
author_facet | Han, Kyung Ah Kim, Jinhu Kim, Hyeonho Kim, Dongwook Lim, Dongseok Ko, Jaewon Um, Ji Won |
author_sort | Han, Kyung Ah |
collection | PubMed |
description | Members of the Slitrk (Slit- and Trk-like protein) family of synaptic cell-adhesion molecules control excitatory and inhibitory synapse development through isoform-dependent extracellular interactions with leukocyte common antigen-related receptor protein tyrosine phosphatases (LAR-RPTPs). However, how Slitrks participate in activation of intracellular signaling pathways in postsynaptic neurons remains largely unknown. Here we report that, among the six members of the Slitrk family, only Slitrk2 directly interacts with the PDZ domain-containing excitatory scaffolds, PSD-95 and Shank3. The interaction of Slitrk2 with PDZ proteins is mediated by the cytoplasmic COOH-terminal PDZ domain-binding motif (Ile-Ser-Glu-Leu), which is not found in other Slitrks. Mapping analyses further revealed that a single PDZ domain of Shank3 is responsible for binding to Slitrk2. Slitrk2 forms in vivo complexes with membrane-associated guanylate kinase (MAGUK) family proteins in addition to PSD-95 and Shank3. Intriguingly, in addition to its role in synaptic targeting in cultured hippocampal neurons, the PDZ domain-binding motif of Slitrk2 is required for Slitrk2 promotion of excitatory synapse formation, transmission, and spine development in the CA1 hippocampal region. Collectively, our data suggest a new molecular mechanism for conferring isoform-specific regulatory actions of the Slitrk family in orchestrating intracellular signal transduction pathways in postsynaptic neurons. |
format | Online Article Text |
id | pubmed-6863843 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-68638432019-11-20 Slitrk2 controls excitatory synapse development via PDZ-mediated protein interactions Han, Kyung Ah Kim, Jinhu Kim, Hyeonho Kim, Dongwook Lim, Dongseok Ko, Jaewon Um, Ji Won Sci Rep Article Members of the Slitrk (Slit- and Trk-like protein) family of synaptic cell-adhesion molecules control excitatory and inhibitory synapse development through isoform-dependent extracellular interactions with leukocyte common antigen-related receptor protein tyrosine phosphatases (LAR-RPTPs). However, how Slitrks participate in activation of intracellular signaling pathways in postsynaptic neurons remains largely unknown. Here we report that, among the six members of the Slitrk family, only Slitrk2 directly interacts with the PDZ domain-containing excitatory scaffolds, PSD-95 and Shank3. The interaction of Slitrk2 with PDZ proteins is mediated by the cytoplasmic COOH-terminal PDZ domain-binding motif (Ile-Ser-Glu-Leu), which is not found in other Slitrks. Mapping analyses further revealed that a single PDZ domain of Shank3 is responsible for binding to Slitrk2. Slitrk2 forms in vivo complexes with membrane-associated guanylate kinase (MAGUK) family proteins in addition to PSD-95 and Shank3. Intriguingly, in addition to its role in synaptic targeting in cultured hippocampal neurons, the PDZ domain-binding motif of Slitrk2 is required for Slitrk2 promotion of excitatory synapse formation, transmission, and spine development in the CA1 hippocampal region. Collectively, our data suggest a new molecular mechanism for conferring isoform-specific regulatory actions of the Slitrk family in orchestrating intracellular signal transduction pathways in postsynaptic neurons. Nature Publishing Group UK 2019-11-19 /pmc/articles/PMC6863843/ /pubmed/31745231 http://dx.doi.org/10.1038/s41598-019-53519-1 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Han, Kyung Ah Kim, Jinhu Kim, Hyeonho Kim, Dongwook Lim, Dongseok Ko, Jaewon Um, Ji Won Slitrk2 controls excitatory synapse development via PDZ-mediated protein interactions |
title | Slitrk2 controls excitatory synapse development via PDZ-mediated protein interactions |
title_full | Slitrk2 controls excitatory synapse development via PDZ-mediated protein interactions |
title_fullStr | Slitrk2 controls excitatory synapse development via PDZ-mediated protein interactions |
title_full_unstemmed | Slitrk2 controls excitatory synapse development via PDZ-mediated protein interactions |
title_short | Slitrk2 controls excitatory synapse development via PDZ-mediated protein interactions |
title_sort | slitrk2 controls excitatory synapse development via pdz-mediated protein interactions |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6863843/ https://www.ncbi.nlm.nih.gov/pubmed/31745231 http://dx.doi.org/10.1038/s41598-019-53519-1 |
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